title: Na+ influx and Na(+)-K+ pump activation during short-term exposure of cardiac myocytes to aldosterone.
abstract: To examine the effect of aldosterone on sarcolemmal Na+ transport, we measured ouabain-sensitive electrogenic Na(+)-K+ pump current (Ip) in voltage-clamped ventricular myocytes and intracellular Na+ activity (alpha iNa) in right ventricular papillary muscles. Aldosterone (10 nM) induced an increase in both Ip and the rate of rise of alpha iNa during Na(+)-K+ pump blockade with the fast-acting cardiac steroid dihydroouabain. The aldosterone-induced increase in Ip and rate of rise of alpha iNa was eliminated by bumetanide, suggesting that aldosterone activates Na+ influx through the Na(+)-K(+)-2Cl- cotransporter. To obtain independent support for this, the Na+, K+, and Cl- concentrations in the superfusate and solution of pipettes used to voltage clamp myocytes were set at levels designed to abolish the inward electrochemical driving force for the Na(+)-K(+)-2Cl- cotransporter. This eliminated the aldosterone-induced increase in Ip. We conclude that in vitro exposure of cardiac myocytes to aldosterone activates the Na(+)-K(+)-2Cl- cotransporter to enhance Na+ influx and stimulate the Na(+)-K+ pump.
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Mihailidou
authors.forename: K A
authors.initials: KA
authors.lastname: Buhagiar
authors.forename: H H
authors.initials: HH
authors.lastname: Rasmussen
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004789:Enzyme Activation; D006352:Heart Ventricles; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D000451:Mineralocorticoid Receptor Antagonists; D010042:Ouabain / Q000031:analogs & derivatives / Q000494:pharmacology; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D028021:Sodium-Potassium-Chloride Symporters; C000977:dihydroouabain; D013779:Tetrodotoxin; D000450:Aldosterone; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase